Project Summary Waterpipe (WP) tobacco smoking has surpassed cigarette smoking and now rivals the electronic cigarette as the most popular tobacco product class in the US among youth. This may be due to the availability of sweet, fruit- and candy-flavored tobaccos that make inhaling tobacco smoke more appealing. It is not clear what is most important in terms of increasing appeal: the smoker's perception of sweetness, or flavor, or both. WP tobacco is unique because of the amounts and identities of its additives and the way that it is smoked. The flavorings and high levels of sweet humectants produce harmful and potentially harmful constituents in the smoke, and are thought to contribute to the direct and indirect harm experienced by users. To define the effects of specific chemical content with respect to sweet perception and likability among users, WP tobacco that differs only in the variables of interest must be used. There is no set of commercially available tobacco brands for which this is true, and thus we propose to manipulate commercial products to properly isolate the important variables. There is an existing data gap surrounding the influence of WP tobacco additives, i.e., sweet humectants and flavorings, on the addictiveness, toxicity, flavor perceptions and appeal of WP smoking. The proposed study uses a crossover human trial, a manipulated WP tobacco prodcut, a validated research grade waterpipe and cutting edge analytical chemistry and psychosocial instruments to systematically investigate the effects of sweet humectant concentration and flavorings on the appeal, puffing behavior, and toxicity of WP tobacco smoking. The purpose of the proposed study is to acquire sound scientific data to inform the development of possible regulatory actions such as identifying and establishing evidenced-based product standards, or maximum thresholds of additives in WP tobacco that must not be exceeded in order for the product to be sold and distributed in the US. This study will address RFA-OD-15-005 questions 3 and 4 by quantifying the impact of WP tobacco additives, such as humectants and flavorants, on human puffing behaviors and HPHC levels in mainstream WP tobacco smoke to address these important data gaps.